Interleukin-3 (IL-3) is one of the cytokines of significance for the regulation of hematopoiesis and inflammation. Recently, we established IL-3-dependent Ba/F3 pro-B cells ectopically expressing RON tyrosine kinase, a receptor for macrophage-stimulating protein (MSP), and showed that MSP stimulation specifically promoted cell morphological changes through tyrosine phosphorylation of the IL-3 common β-chain receptor subunit (βc) by activated RON kinase without activation of JAK2 tyrosine kinase. Here we investigate the IL-3 signaling pathway leading to morphological changes through tyrosine phosphorylation of βc. Treatment of RON-expressing cells with PD98059 or U0126, inhibitors of mitogen-activated protein kinase kinase activity, blocked both IL-3- and MSP-induced morphological changes. Upon stimulation with IL-3 or MSP, extracellular-regulated kinase (ERK) and F-actin were redistributed in uropod-like structures. ERK and F-actin were colocalized within uropod-like structures, and a majority of F-actin were localized around the peripheries of accumulated ERK. Tyrosine phosphorylation of ERK was detected after stimulation with IL-3 or MSP, whereas treatment with U0126 specifically inhibited IL-3- or MSP-induced ERK phosphorylation but not tyrosine phosphorylation of βc. These results suggest that the activation and localization of ERK to uropod-like structures play a role in IL-3-induced morphological changes.
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